Atg5 Is Essential for the Development and Survival of Innate Lymphocytes
Autophagy is an essential cellular survival mechanism that is required for adaptive lymphocyte development; however, its role in innate lymphoid cell (ILC) development remains unknown. Furthermore, the conditions that promote lymphocyte autophagy during homeostasis are poorly understood. Here, we de...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-05-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716305277 |
| _version_ | 1828406145282211840 |
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| author | Timothy E. O’Sullivan Clair D. Geary Orr-El Weizman Theresa L. Geiger Moritz Rapp Gerald W. Dorn II Michael Overholtzer Joseph C. Sun |
| author_facet | Timothy E. O’Sullivan Clair D. Geary Orr-El Weizman Theresa L. Geiger Moritz Rapp Gerald W. Dorn II Michael Overholtzer Joseph C. Sun |
| author_sort | Timothy E. O’Sullivan |
| collection | DOAJ |
| description | Autophagy is an essential cellular survival mechanism that is required for adaptive lymphocyte development; however, its role in innate lymphoid cell (ILC) development remains unknown. Furthermore, the conditions that promote lymphocyte autophagy during homeostasis are poorly understood. Here, we demonstrate that Atg5, an essential component of the autophagy machinery, is required for the development of mature natural killer (NK) cells and group 1, 2, and 3 innate ILCs. Although inducible ablation of Atg5 was dispensable for the homeostasis of lymphocyte precursors and mature lymphocytes in lymphoreplete mice, we found that autophagy is induced in both adaptive and innate lymphocytes during homeostatic proliferation in lymphopenic hosts to promote their survival by limiting cell-intrinsic apoptosis. Induction of autophagy through metformin treatment following homeostatic proliferation increased lymphocyte numbers through an Atg5-dependent mechanism. These findings highlight the essential role for autophagy in ILC development and lymphocyte survival during lymphopenia. |
| first_indexed | 2024-12-10T11:06:12Z |
| format | Article |
| id | doaj.art-a5f3f3d094ee40ddb4b92e8afff41133 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T11:06:12Z |
| publishDate | 2016-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-a5f3f3d094ee40ddb4b92e8afff411332022-12-22T01:51:32ZengElsevierCell Reports2211-12472016-05-011591910191910.1016/j.celrep.2016.04.082Atg5 Is Essential for the Development and Survival of Innate LymphocytesTimothy E. O’Sullivan0Clair D. Geary1Orr-El Weizman2Theresa L. Geiger3Moritz Rapp4Gerald W. Dorn II5Michael Overholtzer6Joseph C. Sun7Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USACenter for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63105, USACell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAImmunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAAutophagy is an essential cellular survival mechanism that is required for adaptive lymphocyte development; however, its role in innate lymphoid cell (ILC) development remains unknown. Furthermore, the conditions that promote lymphocyte autophagy during homeostasis are poorly understood. Here, we demonstrate that Atg5, an essential component of the autophagy machinery, is required for the development of mature natural killer (NK) cells and group 1, 2, and 3 innate ILCs. Although inducible ablation of Atg5 was dispensable for the homeostasis of lymphocyte precursors and mature lymphocytes in lymphoreplete mice, we found that autophagy is induced in both adaptive and innate lymphocytes during homeostatic proliferation in lymphopenic hosts to promote their survival by limiting cell-intrinsic apoptosis. Induction of autophagy through metformin treatment following homeostatic proliferation increased lymphocyte numbers through an Atg5-dependent mechanism. These findings highlight the essential role for autophagy in ILC development and lymphocyte survival during lymphopenia.http://www.sciencedirect.com/science/article/pii/S2211124716305277 |
| spellingShingle | Timothy E. O’Sullivan Clair D. Geary Orr-El Weizman Theresa L. Geiger Moritz Rapp Gerald W. Dorn II Michael Overholtzer Joseph C. Sun Atg5 Is Essential for the Development and Survival of Innate Lymphocytes Cell Reports |
| title | Atg5 Is Essential for the Development and Survival of Innate Lymphocytes |
| title_full | Atg5 Is Essential for the Development and Survival of Innate Lymphocytes |
| title_fullStr | Atg5 Is Essential for the Development and Survival of Innate Lymphocytes |
| title_full_unstemmed | Atg5 Is Essential for the Development and Survival of Innate Lymphocytes |
| title_short | Atg5 Is Essential for the Development and Survival of Innate Lymphocytes |
| title_sort | atg5 is essential for the development and survival of innate lymphocytes |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716305277 |
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